Mechanisms concerned in the direct effect of isoflurane on rat hippocampal and human neocortical neurons.
The effect of isoflurane on postsynaptic neurons was studied by intracellular recordings from rat hippocampus and human neocortex in vitro. Isoflurane caused a hyperpolarization of the cell membrane. The hyperpolarization was reversed (although incompletely in some neurons) by increasing the membrane potential. The reversal potential was -80 +/- 12 mV (mean +/- S.D.) or 12 +/- 6 mV negative to the resting membrane potential. Potassium channel blockers reduced the isoflurane-induced hyperpolarization, while chloride loading was without effect. The transient depolarization preceding the hyperpolarization in some of the neurons was not reversed by hyperpolarization. The action potential was prolonged by 19 +/- 3% due to a slower rate of rise. The rise time was almost doubled. Firing threshold was increased by 4 +/- 3 mV (relative to the reference electrode). Subthreshold inward rectification was reduced or abolished. Some cells showed subthreshold outward rectification during isoflurane administration. These results suggest that isoflurane depressed neuronal excitability by (1) hyperpolarizing the cell membrane, at least partly by an increase in potassium conductance, (2) slowing the rate of rise of the action potential, presumably due to interference with the fast sodium channel, (3) decreasing subthreshold inward rectification and (4) increasing firing threshold.
Berg-Johnsen
J
J
University of Oslo, Department of Neurosurgery, Ullevaal Hospital, Norway.
Langmoen
I A
IA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D007530:Isoflurane